Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

Publication date: 11 October 2017
Source:Cell Host & Microbe, Volume 22, Issue 4
Author(s): H.-Heinrich Hoffmann, William M. Schneider, Vincent A. Blomen, Margaret A. Scull, Alain Hovnanian, Thijn R. Brummelkamp, Charles M. Rice
Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxoviridae, Flaviviridae, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the trans-Golgi network that require calcium for their activity and are critical for virus glycoprotein maturation. Consistent with these findings, viral glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread, which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an attractive antiviral host target for a broad spectrum of established and emerging viral infections.

Graphical abstract

Teaser

In this issue of Cell Host & Microbe, Hoffmann et al. determine that the calcium pump, SPCA1, is required for virus spread. Loss of SPCA1 reduces activity of calcium-dependent proteases in the trans-Golgi network and consequently hinders viral glycoprotein maturation. Thus, SPCA1 is an attractive host target for viral infections.


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